The bacterial melibiose permease (MelB) belongs to the glycoside-pentoside-hexuronide:cation symporter family, a part of the major facilitator superfamily (MFS). Structural information regarding ...glycoside-pentoside-hexuronide:cation symporter family transporters and other Na(+)-coupled permeases within MFS has been lacking, although a wealth of biochemical and biophysical data are available. Here we present the three-dimensional crystal structures of Salmonella typhimurium MelBSt in two conformations, representing an outward partially occluded and an outward inactive state of MelBSt. MelB adopts a typical MFS fold and contains a previously unidentified cation-binding motif. Three conserved acidic residues form a pyramidal-shaped cation-binding site for Na(+), Li(+) or H(+), which is in close proximity to the sugar-binding site. Both cosubstrate-binding sites are mainly contributed by the residues from the amino-terminal domain. These two structures and the functional data presented here provide mechanistic insights into Na(+)/melibiose symport. We also postulate a structural foundation for the conformational cycling necessary for transport catalysed by MFS permeases in general.
The antenatal, intrapartum, and postnatal periods are considered high-risk periods for the health of mothers and their newborns. Although the current utilization rate of some maternal and child care ...services in Jordan is encouraging, detailed information about the quality of these services is limited. Therefore, this study aimed to explore the quality of maternal-fetal and newborn antenatal care (ANC), delivery, and postnatal care (PNC) services in Jordan.
We conducted 12 focus group discussions (FGDs) with pregnant and postpartum women who attended maternal-child care services in three major hospitals in Jordan. All FGDs were recorded and transcribed verbatim. An inductive thematic analysis approach was used to identify themes and subthemes.
The content analysis of the FGDs revealed a consensus among the discussants regarding the importance of ANC and PNC services for the health of mothers and their newborns. However, the participating women viewed ANC to be much more important than PNC. With regards to the choice between public and private antenatal care services, some of the discussants were disposed towards the private sector. Reasons for this included longer consultation time, a higher quality of services, better interpersonal and communication skills of healthcare providers, better treatment, more advanced equipment and devices, availability of female obstetricians, and more flexible appointment times. These women only perceived public hospital services to be necessary in cases of pregnancy-related complications and labor, as the costs of private sector services in such cases are too high. The findings also revealed that mothers usually only seek PNC services to check up on their newborn's health and not their own.
Visiting private ANC clinics throughout pregnancy while giving birth in public facilities leads to the discontinuity and fragmentation in maternal-fetal and child healthcare services. To address this fragmentation, healthcare systems are proposed to establish interprofessional teamwork that requires different healthcare providers with complementary skills and practices in both public and private settings to work co-operatively and collectively. Investment in new technologies and interventions which enhance coordination and collaboration between public and private healthcare settings is necessary for the provision of non-traditional maternal healthcare.
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•Orexinergic transmission regulates both nociception and arousal level.•Orexin receptors are expressed in both pain and sleep modulating centers.•Orexins promote analgesia and arousal ...through affecting shared neuronal mechanisms.•Induction of analgesia and wakefulness by orexin might favor survival during stress.•Imbalanced orexin level causes bidirectional dysregulation of sleep-pain processing.
Accumulating evidence support the critical role of endogenous orexin system in modulation of various physiological functions. Among these, regulation of pain and wakefulness have extensively been investigated, however, by independent series of studies each focusing a distinct side. It is now well established that orexins induce potent analgesic effect via affecting their receptors within several specific brain structures. These mainly include locus coeruleus (LC), lateral paragigantocellularis (LPGi), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), periaquiductal gray (PAG) and tuberomammillary nuclei (TMN). On the other hand, increased activity of orexinergic neurons enhances general wakefulness. Interestingly, a review of literature reveals that brain regions underlying orexin-mediated analgesia are most probably the site of action for orexin wake-promoting effects as well. The present study first pieces together the existing evidence supporting the rationale for the possibility of sleep-pain coregulation by orexin system and then suggests several shared mechanisms through which orexin can control the two mentioned processes. Furthermore, this study explains how imbalanced orexinergic transmission can cause progressive dysregulation of sleep-pain processing.
Objective:
To determine if there was an increase in the rate of cases presenting with rhino-orbital-cerebral mucormycosis (ROCM) to a tertiary care center during the first wave of the coronavirus ...disease 2019 (COVID-19) pandemic and the characteristics of the presenting cases.
Methods:
Retrospective observational study reviewing ROCM cases presenting from March 25 until September 25, 2020. Cases fulfilling the clinical, radiological, and pathological/microbiological criteria for diagnosis with ROCM were included. The number of cases presenting during the designated interval, their COVID-19 status, comorbidities, and clinical presentation were analyzed. The number of cases during the corresponding interval in the previous 3 years was used as reference to detect if there was a recent spike.
Results:
Of the 12 ROCM cases identified, 5 had a concurrent positive reverse transcription PCR (RT-PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS
-
CoV
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2), 1 had a prior positive result, and 6 did not have concurrent nor prior positive test results. Nine of the 12 cases had poorly controlled diabetes mellitus, and 2 cases had a hematological malignancy. All cases had orbital invasion, and eight cases had cerebral invasion. The number of cases identified during the interval is much higher than the numbers presenting in the prior 3 years during equivalent intervals (range, one to two cases) than those reported in the literature in different settings in the pre-pandemic era.
Conclusions:
There is an increased rate of ROCM cases presenting to our center during the first wave of the COVID-19 pandemic. This is a preliminary report, and further studies are needed to corroborate the findings and explain possible underlying links.
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•Green synthesis of Cu NPs using aqueous extract of the Otostegia persica leaves.•The Cu NPs were characterized by TEM, FT-IR, UV–vis and XRD.•The synthesized Cu NPs by this method ...are quite stable and can be kept for one month.•One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles in EtOH at room temperature.
In this study, copper nanoparticles (Cu NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of CuCl2·2H2O solution with aqueous extract of leaves of Otostegia persica containing flavonoid and other phenolics as a main factor which acts as reducing agent and efficient stabilizer. UV–vis spectra gave surface plasmon resonance (SPR) at 560nm. The Cu NPs were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). A possible synthesis mechanism of Cu NPs was presented. In addition, we investigated the catalytic activity of Cu NPs for the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles under mild reaction conditions with good to excellent yields. The catalyst could be easily recovered by centrifugation and reused at least five recycles with no significant decreases in the yields.
Recent advances in materials science and engineering highlight the importance of designing sophisticated biomaterials with well-defined architectures and tunable properties for emerging biomedical ...applications. Click chemistry, a powerful method allowing specific and controllable bioorthogonal reactions, has revolutionized our ability to make complex molecular structures with a high level of specificity, selectivity, and yield under mild conditions. These features combined with minimal byproduct formation have enabled the design of a wide range of macromolecular architectures from quick and versatile click reactions. Furthermore, copper-free click chemistry has resulted in a change of paradigm, allowing researchers to perform highly selective chemical reactions in biological environments to further understand the structure and function of cells. In living systems, introducing clickable groups into biomolecules such as polysaccharides (PSA) has been explored as a general approach to conduct medicinal chemistry and potentially help solve healthcare needs. De novo biosynthetic pathways for chemical synthesis have also been exploited and optimized to perform PSA-based bioconjugation inside living cells without interfering with their native processes or functions. This strategy obviates the need for laborious and costly chemical reactions which normally require extensive and time-consuming purification steps. Using these approaches, various PSA-based macromolecules have been manufactured as building blocks for the design of novel biomaterials. Clickable PSA provide a powerful and versatile toolbox for biomaterials scientists and will increasingly play a crucial role in the biomedical field. Specifically, bioclick reactions with PSA have been leveraged for the design of advanced drug delivery systems and minimally invasive injectable hydrogels. In this review article, we have outlined the key aspects and breadth of PSA-derived bioclick reactions as a powerful and versatile toolbox to design advanced polymeric biomaterials for biomedical applications such as molecular imaging, drug delivery, and tissue engineering. Additionally, we have also discussed the past achievements, present developments, and recent trends of clickable PSA-based biomaterials such as three dimensional printing, as well as their challenges, clinical translatability, and future perspectives.
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ObjectiveDuring COVID-19 pandemic, complete lockdown of cities was one of the measures implemented by governments worldwide. Lockdown had a significant impact on people’s lifestyles and access and ...utilisation of health services. This study aimed to assess the impact of the lockdown on glycaemic control among patients with type 2 diabetes mellitus (T2DM).Design and settingThis was a retrospective study, electronic medical records at a leading University Hospital in Northern Jordan were used to extract study data.ParticipantsAll outpatients with T2DM.Primary and secondary outcome measuresGlycated haemoglobin (HbA1c), blood glucose and lipid profile for patients with T2DM, 6 months before and 6 months after the full COVID-19 lockdown.ResultsA total of 639 patients (289 (45.2%) males and 350 (54.8%) females) were included in this study. Their age ranged from 18 to 91 years, with a mean (SD) of 59.9 (13.8) years. The overall means of HbA1c (8.41 vs 8.20, <0.001), high-density lipoprotein (1.16 vs 1.12, <0.001), low-density lipoprotein (2.81 vs 2.49, <0.001) and total cholesterol (4.45 vs 4.25, p<0.001) levels were significantly higher in the period before lockdown compared with the period after the lockdown. However, triglyceride and fasting blood glucose levels were not affected significantly after the lockdown.ConclusionsThe glycaemic control and lipid profile had significantly improved after COVID-19 pandemic lockdown. The availability of medication and medical advice delivery systems (monthly medicine deliveries) during the lockdown in Jordan might have positive impact on patients with diabetes.
An engineered variant of T4 lysozyme serves as a model for studying induced remote conformational changes in a full protein context. The design involves a duplicated surface helix, flanked by two ...loops, that switches between two different conformations spanning about 20 Å. Molecular dynamics simulations of the engineered protein, up to 1 μs, rule out α‐helix to β‐sheet transitions within the duplicated helix as suggested by others. These simulations highlight how the use of different force fields can lead to radical differences in the structure of the protein. In addition, Markov state modeling and transition path theory were employed to map a 6.6 μs simulation for possible early intermediate states and to provide insights into the onset of the switching motion. The putative intermediates involve the folding of one helical turn in the C‐terminal loop through energy driven, sequential rearrangement of nearby salt bridges around the key residue Arg63. These results provide a first step towards understanding the energetics and dynamics of a rather complicated intra‐protein motion.
Abstract
Background
Annually, 2.6 million stillbirths occur around the world, with approximately 98% occurring in low- and middle-income countries. The stillbirth rates in these countries are 10 ...times higher than the rates in high-income countries.
Methods
An electronic stillbirths and neonatal deaths surveillance system (JSANDS) was established in five large hospitals located in three of the largest cities in Jordan in August 2019. JSANDS was developed as a secure on-line data entry system to collect, organize, analyze, and disseminate data on stillbirths, neonatal deaths, and their contributing conditions. Data on births, stillbirths and their contributing conditions, and other demographic and clinical characteristics in the period between August 2019 – January 2020 were extracted and analyzed.
Results
A total of 10,328 births were registered during the reporting period. Of the total births, 102 were born dead (88 antepartum stillbirths and 14 intrapartum stillbirths), with a rate of 9.9 per 1000 total births. The main contributing fetal conditions of antepartum stillbirths were antepartum death of unspecified cause (33.7%), acute antepartum event (hypoxia) (33.7%), congenital malformations and chromosomal abnormalities (13.3%), and disorders related to the length of gestation and fetal growth (10.8%). The main contributing maternal conditions of antepartum stillbirths included complications of the placental cord and membranes (48.7%), maternal complications of pregnancy (23.1%), and maternal medical and surgical conditions (23.1%). Contributing fetal conditions of intrapartum stillbirths included congenital malformations, deformations and chromosomal abnormalities, other specified intrapartum disorders, and intrapartum death of unspecified cause (33.3% each). Contributing maternal conditions of intrapartum stillbirths included complications of the placental cord and membranes. In the multivariate analysis, small for gestational age (SGA) pregnancies were associated with a significant 3-fold increased risk of stillbirth compared to appropriate for gestational age (AGA) pregnancies.
Conclusions
Although the rate of stillbirth is lower than that in other countries in the region, there is an opportunity to prevent such deaths. While the majority of stillbirths occurred during the antepartum period, care should be taken for the early identification of high-risk pregnancies, including the early detection of SGA pregnancies, and ensuring adequate antenatal obstetric interventions.
Public acceptance of governmental measures are key to controlling the spread of infectious diseases. The COVID-19 pandemic has placed a significant burden on healthcare systems for high-income ...countries as well as low- and middle-income countries (LMICs). The ability of LMICs to respond to the challenge of the COVID-19 pandemic has been limited and may have affected the impact of governmental strategies to control the spread of COVID-19. This study aimed to evaluate and compare public opinion on the governmental COVID-19 response of high and LMICs in the Middle East and benchmark it to international countries.
An online, self-administered questionnaire was distributed among different Middle Eastern Arab countries. Participants' demographics and level of satisfaction with governmental responses to COVID-19 were analyzed and reported. Scores were benchmarked against 19 international values.
A total of 7395 responses were included. Bahrain scored highest for satisfaction with the governmental response with 38.29 ± 2.93 on a scale of 40, followed by the Kingdom of Saudi Arabia (37.13 ± 3.27), United Arab Emirates (36.56 ± 3.44), Kuwait (35.74 ± 4.85), Jordan (23.08 ± 6.41), and Lebanon (15.39 ± 5.28). Participants' country of residence was a significant predictor of the satisfaction score (P < 0.001), and participants who suffered income reduction due to the pandemic, had a history of SARS-CoV-2 infection, and held higher educational degrees had significantly lower satisfaction scores (P < 0.001). When benchmarked with other international publics, countries from the Gulf Cooperation Council had the highest satisfaction level, Jordan had an average score, and Lebanon had one of the lowest satisfaction scores.
The political crisis in Lebanon merged with the existing corruption were associated with the lowest public satisfaction score whereas the economical instability of Jordan placed the country just before the lowest position. On the other hand, the solid economy plus good planning and public trust in the government placed the other countries of the Gulf Cooperation Council on top of the scale. Further investigation is necessary to find out how the governments of other low-income countries may have handled the situation wisely and gained the trust of their publics. This may help convey a clearer picture to Arab governments that have suffered during the pandemic.